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Drug Delivery and Translational Research Feb 2018The oral bioavailability of felodipine, a dihydropyridine calcium channel antagonist, is about 15%. This may be due to poor water solubility, and a lower intestinal...
The oral bioavailability of felodipine, a dihydropyridine calcium channel antagonist, is about 15%. This may be due to poor water solubility, and a lower intestinal permeability than a BCS class I drug, and hepatic first-pass metabolism of the drug. Many drugs are unpopular due to solubility issues. The goal of this study was to develop and optimize a felodipine-containing microemulsion to improve the intestinal permeability and bioavailability of the drug. The felodipine microemulsions were developed with the selected components, i.e., α-linolenic acid as the oil phase, Tween 80 as a surfactant, and isopropyl alcohol as co-surfactant using Box-Behnken design and characterized for in vitro release and particle size. The optimized felodipine-loaded microemulsion was investigated for physicochemical interaction, surface morphology, intestinal permeability, rheology, cytotoxicity, cellular uptake, pharmacodynamic (electrocardiogram and heart rate variability), and pharmacokinetic studies to explore its suitability as a promising oral drug delivery system for the treatment of hypertension. The optimized felodipine-loaded microemulsion showed significantly higher (P < 0.05) apparent permeability coefficients (Papp) at 7.918 × 10 cm/s after 1 h, when compared with conventional formulations that are marketed tablet, drug oily solution, and drug emulsion, which showed a maximum Papp of 3.013, 4.428, and 5.335 × 10 cm/s, respectively. The optimized felodipine-loaded microemulsion showed biocompatibility and no cytotoxicity. Cellular uptake studies confirmed payload delivery to a cellular site on the J774.A1 cell line. The rheology study of the optimized felodipine-loaded microemulsion revealed Newtonian-type flow behavior and discontinuous microemulsion formation. In pharmacodynamic studies, significant differences in parameters were observed between the optimized felodipine-loaded microemulsion and marketed formulation. The optimized felodipine-loaded microemulsion showed significantly higher (p < 0.01) C (7.12 ± 1.04 μg/ml) than marketed tablets (2.44 ± 1.03 μg/ml). It was found that AUC obtained from the optimized felodipine-loaded microemulsion (84.53 ± 10.73 μg h/ml) was significantly higher (p < 0.01) than the marketed tablet (27.41 ± 5.54 μg h/ml). The relative bioavailability (Fr) of the optimized felodipine-loaded microemulsion was about 308.3% higher than that of the marketed formulation. The results demonstrate that the prepared microemulsion is an advanced and efficient oral delivery system of felodipine for the management of hypertension.
Topics: Administration, Oral; Animals; Biological Availability; Calcium Channel Blockers; Cell Line; Cell Survival; Chemistry, Pharmaceutical; Drug Delivery Systems; Drug Liberation; Emulsions; Felodipine; Heart Rate; Intestinal Absorption; Mice; Rats, Wistar; alpha-Linolenic Acid
PubMed: 29204927
DOI: 10.1007/s13346-017-0453-9 -
Clinics (Sao Paulo, Brazil) Oct 2018Dietary omega-3 fatty acids have been efficacious in decreasing serum cholesterol levels and reducing the risk of cardiovascular disease. However, the metabolic and...
OBJECTIVES
Dietary omega-3 fatty acids have been efficacious in decreasing serum cholesterol levels and reducing the risk of cardiovascular disease. However, the metabolic and molecular changes induced by the omega-3 fatty acid α-linolenic acid (ALA), which is found in linseed oil, are not fully understood. In this study, we showed a correlation between ALA and insulin resistance, inflammation and endoplasmic reticulum stress (ERS).
METHODS
We studied 40 male mice (C57/BL6) divided into 4 groups: a control (C) group, a control + omega-3/ALA (CA) group, a high-fat diet (HFD) (H) group and a high-fat diet + omega-3/ALA (HA) group. For 8 weeks, the animals in the H and HA groups were fed a high-fat (60%) diet, while the animals in the C and CA groups received regular chow. The diets of the CA and HA groups were supplemented with 10% lyophilized ALA.
RESULTS
ALA supplementation improved glucose tolerance and reduced insulin resistance, as measured by intraperitoneal glucose tolerance tests and the homeostasis model assessment for insulin resistance, respectively. In addition, ALA reduced hepatic steatosis and modified the standard fat concentration in the liver of animals fed an HFD. Dietary ALA supplementation reduced the serum levels of interleukin 6 (IL-6), interleukin 1 beta (IL-1β) and monocyte chemoattractant protein-1 (MCP-1), increased the expression of important chaperones such as binding immunoglobulin protein (BIP) and heat shock protein 70 (HSP70) and reduced the expression of C/EBP-homologous protein (CHOP) and X-box binding protein 1 (XBP1) in hepatic tissues, suggesting an ERS adaptation in response to ALA supplementation.
CONCLUSIONS
Dietary ALA supplementation is effective in preventing hepatic steatosis; is associated with a reduction in insulin resistance, inflammation and ERS; and represents an alternative for improving liver function and obtaining metabolic benefits.
Topics: Animals; Diet, High-Fat; Dietary Supplements; Endoplasmic Reticulum Stress; Fatty Acids, Omega-3; Fatty Liver; Glucose Tolerance Test; Inflammation; Insulin Resistance; Male; Mice; Mice, Inbred C57BL; alpha-Linolenic Acid
PubMed: 30379219
DOI: 10.6061/clinics/2018/e150 -
The British Journal of Nutrition Jul 2016The regulation of lipogenesis mechanisms related to consumption of n-3 PUFA is poorly understood. The aim of the present study was to find out whether α-linolenic acid...
The regulation of lipogenesis mechanisms related to consumption of n-3 PUFA is poorly understood. The aim of the present study was to find out whether α-linolenic acid (ALA) or DHA uptake can have an effect on activities and gene expressions of enzymes involved in lipid metabolism in the liver, subcutaneous adipose tissue and longissimus dorsi (LD) muscle of growing-finishing pigs. Six groups of ten pigs received one of six experimental diets supplemented with rapeseed oil in the control diet, extruded linseed, microalgae or a mixture of both to implement different levels of ALA and DHA with the same content in total n-3. Results were analysed for linear and quadratic effects of DHA intake. The results showed that activities of malic enzyme (ME) and fatty acid synthase (FAS) decreased linearly in the liver with dietary DHA. Although the expression of the genes of these enzymes and their activities were poorly correlated, ME and FAS expressions also decreased linearly with DHA intake. The intake of DHA down-regulates the expressions of other genes involved in fatty acid (FA) metabolism in some tissues of pigs, such as fatty acid desaturase 2 and sterol-regulatory element binding transcription factor 1 in the liver and 2,4-dienoyl CoA reductase 2 in the LD muscle. FA oxidation in the LD muscle and FA synthesis decreased in the liver with increasing amount of dietary DHA, whereas a retroconversion of DHA into EPA seems to be set up in this last tissue.
Topics: Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Diet; Docosahexaenoic Acids; Fatty Acid Synthases; Female; Gene Expression Regulation; Lipid Metabolism; Lipogenesis; Male; Swine; alpha-Linolenic Acid
PubMed: 27181335
DOI: 10.1017/S0007114516001392 -
Journal of the International Society of... Nov 2020Among n-3 polyunsaturated fatty acids (PUFAs), the most important is α-linolenic acid (ALA). The biological activity of ALA is not equivalent to that of the long-chain...
BACKGROUND
Among n-3 polyunsaturated fatty acids (PUFAs), the most important is α-linolenic acid (ALA). The biological activity of ALA is not equivalent to that of the long-chain n-3 PUFAs, and it has pleiotropic effects, such as functioning as an energy substrate during long-term training when carbohydrate reserves are depleted. The purpose of this investigation was to study the link between the essential dietary and plasma ALA and aerobic performance, which is estimated via maximal fat oxidation (MFO), among skiers.
METHODS
Twenty-four highly trained male athletes from the Russian cross-country skiing team participated in the study. ALA intake was determined by an original program used to assess the actual amount and frequency of fat consumption. The plasma level of ALA was determined using gas-liquid chromatography. The skiers' aerobic performance was estimated via MFO and determined by indirect calorimetry using the system "Oxycon Pro".
RESULTS
The consumption of ALA in the diet in half of the skiers was below the recommended level at 0.5 ± 0.2 g/day. The deficiency of plasma ALA levels was on average 0.2 ± 0.1 Mol% for almost all participants. The consumption of ALA in the diet and its level in plasma were associated with MFO (r = 0.507, p = 0.011; r = 0.460, p = 0.023). Levels of ALA in plasma (p = 0.0523) and the consumption of ALA in the diet (p = 0.0039) were associated with high aerobic performance.
CONCLUSIONS
ALA in the diet of the athletes may be used as nutritional support to increase MFO and aerobic performance.
Topics: Adult; Athletic Performance; Calorimetry, Indirect; Dietary Fats; Exercise; Exercise Test; Heart Rate; Humans; Lipids; Male; Oxidation-Reduction; Recommended Dietary Allowances; Russia; Skiing; Sports Nutritional Physiological Phenomena; Young Adult; alpha-Linolenic Acid
PubMed: 33198755
DOI: 10.1186/s12970-020-00385-2 -
Journal of the Science of Food and... Sep 2020Medium- and long- chain triacylglycerols (MLCTs) are functional structural lipids that can provide the human body with essential fatty acids and a faster energy supply....
BACKGROUND
Medium- and long- chain triacylglycerols (MLCTs) are functional structural lipids that can provide the human body with essential fatty acids and a faster energy supply. This study aimed to prepare MLCTs rich in α-linolenic by enzymatic interesterification of perilla oil and medium-chain triacylglycerols (MCTs), catalyzed by Lipozyme RM IM, Lipozyme TL IM, Lipozyme 435, and Novozyme 435 respectively.
RESULTS
The effects of lipase loading, concentration of MCTs, reaction temperature, and reaction time on the yield of MLCTs were investigated. It was found that the reaction achieved more than a 70% yield of MLCTs in triacylglycerols under the conditions of 400 g kg MCTs and 60 g kg lipase loading after equilibrium. A novel two-stage deodorization was also applied to purify the interesterification products. The triacylglycerols reach over 97% purity in the products with significant removal (P < 0.05) of the free fatty acids, and the trans fatty acids were strictly controlled at below 1%. There was more than 40% α-linolenic in the purified products, with long-chain fatty acids mostly occupying the desired sn-2 position in acylglycerols, which are more active in hydrolysis.
CONCLUSION
A series of novel α-linolenic acid-rich medium- and long-chain triacylglycerols was prepared. Under appropriate reaction conditions, the yield of MLCTs in triacylglycerols was above 70%. A novel two-stage deodorization can be used to promote the elimination of free fatty acids and limit the generation of trans fatty acids. © 2020 Society of Chemical Industry.
Topics: Biocatalysis; Enzymes, Immobilized; Fatty Acids; Fungal Proteins; Lipase; Plant Oils; Triglycerides; alpha-Linolenic Acid
PubMed: 32419135
DOI: 10.1002/jsfa.10515 -
Food & Function Mar 2021α-Linolenic acid (ALA) is recognised to have a regulatory effect on cardiovascular diseases. Due to the low bioavailability of linseed oil (LINO), which is the most...
α-Linolenic acid (ALA) is recognised to have a regulatory effect on cardiovascular diseases. Due to the low bioavailability of linseed oil (LINO), which is the most common ALA supplement, it is necessary to find a replacement for ALA supplements that is more easily accepted by the human body. The content of ALA in silkworm pupae oil (SPO) is 32.60 ± 0.67%, and SPO can be substituted as a dietary lipid to meet the demand of the human body. In the present study, a pH-stat system was used to investigate the release degree of free fatty acids (FFAs) from SPO and construct a first-order kinetic model. Digestion experiments in vitro with different lipids showed that the maximum release FFA levels were SPO > SO (soybean oil) > LO (lard oil) > MSO (mulberry seed oil) > LINO, and the first-order kinetic apparent rate constants were LINO > SPO > LO > SO > MSO. Triacylglycerol (TAG) and fatty acid composition are the decisive factors in determining the level of lipid digestion. Therefore, the maximum level of FFAs released from SPO (84.34 ± 1.37%) was much higher than that of LINO (49.78 ± 0.52%) when the hydrolysis rates were 0.2114 s and 0.2249 s, respectively. In addition, the smaller emulsion droplet size (609.24 ± 43.46 nm) and weaker surface charge (-17.93 ± 0.42 mV) also resulted in higher levels of SPO under in vitro digestion conditions. Meanwhile, due to low melting and crystallisation temperature, SPO is quickly absorbed by the human body. Overall, SPO can be used as a new alternative for ALA supplements based on its superior digestive properties.
Topics: Animals; Bombyx; Dietary Supplements; Digestion; Fatty Acids; Humans; Hydrogen-Ion Concentration; Models, Biological; Particle Size; Plant Oils; Pupa; Triglycerides; alpha-Linolenic Acid
PubMed: 33624675
DOI: 10.1039/d0fo03469j -
The American Journal of Clinical... Oct 2001Data on the relation between alpha-linolenic acid intake and coronary artery disease (CAD) are limited. Other dietary components appear to modify the reported relation...
BACKGROUND
Data on the relation between alpha-linolenic acid intake and coronary artery disease (CAD) are limited. Other dietary components appear to modify the reported relation between alpha-linolenic acid intake and CAD.
OBJECTIVE
We examined whether dietary alpha-linolenic acid intake was inversely associated with risk of CAD.
DESIGN
We prospectively studied 667 men aged 64-84 y from the Zutphen Elderly Study who were free of CAD at baseline. Dietary intake was assessed by using a cross-check dietary history method.
RESULTS
During the 10-y follow-up, we documented 98 cases of CAD. After adjustment for age, standard coronary risk factors, and intake of trans fatty acids and other nutrients, alpha-linolenic acid intake was not significantly associated with CAD risk. The relative risk of CAD for the highest compared with the lowest tertile of alpha-linolenic acid intake was 1.68 (95% CI: 0.86, 3.29). alpha-Linolenic acid intake from sources containing trans fatty acids was also nonsignificantly, yet positively, associated with CAD risk. alpha-Linolenic acid intake from foods that did not contain trans fatty acids was not associated with CAD risk, the relative risk of CAD for the highest compared with the lowest tertile was 1.15 (95% CI: 0.63, 2.11).
CONCLUSION
We did not observe a beneficial effect of dietary alpha-linolenic acid intake on the risk of 10-y CAD incidence. Investigating this hypothesis was complicated by the association between intakes of alpha-linolenic acid and trans fatty acids. Given the results of current prospective studies, a protective cardiac effect of alpha-linolenic acid is questionable.
Topics: Aged; Aged, 80 and over; Blood Pressure; Cholesterol; Coronary Disease; Diet; Dietary Fats; Humans; Incidence; Male; Netherlands; Risk Factors; alpha-Linolenic Acid
PubMed: 11566643
DOI: 10.1093/ajcn/74.4.457 -
Wei Sheng Yan Jiu = Journal of Hygiene... Jul 2018To investigate the bioavailability of heavy metal cadmium on planktonic algae under the condition of containing linolenic acid.
OBJECTIVE
To investigate the bioavailability of heavy metal cadmium on planktonic algae under the condition of containing linolenic acid.
METHODS
Using different concentrations of Cd~(2+)( 0. 10, 0. 20, 0. 30 and 0. 40 mg/L) alone, as well as different combinations of cadmium with 0. 01 mL/L linolenic acid that acted on Scenedesmus obliquus and Microcystis aeruginosa respectively, then the growth-inhibitory of S. obliquus and M. aeruginosa and the absorption of cadmium and adsorption of cadmium by S. obliquus and M. aeruginosa were detected.
RESULTS
Both cadmium alone and linolenic acid alone had certain inhibitory effects on M. aeruginosa and S. obliquus at the concentrations, and the inhibition was stronger on M. aeruginosa. The inhibition rates reached 42. 17% and 67. 42% of 0. 10 and 0. 40 mg/L Cd~(2+) at the 96 h, the inhibition rate of 0. 01 mL/L linolenic acid at the 96 h was 39. 33%, there were no changes with the inhibitory effects when linolenic acid and cadmium coexisted. But both the cadmium uptake and adsorption amount by M. aeruginosa and S. obliquus all decreased under the condition of containing linolenic acid( P < 0. 05).
CONCLUSION
The fatty acid carboxyl may have mild chelation to cadmium ions, which can reduce the heavy metal cadmium toxicity, and also reduce the uptake or absorption of cadmium by algae cells.
Topics: Biological Availability; Cadmium; Microcystis; Scenedesmus; Surface-Active Agents; Water; alpha-Linolenic Acid
PubMed: 30081995
DOI: No ID Found -
Journal of Oleo Science 2024Conjugated fatty acids have anticancer effects. Therefore, the establishment of a synthetic method for conjugated fatty acids is important for overcoming cancer. Here,...
Conjugated fatty acids have anticancer effects. Therefore, the establishment of a synthetic method for conjugated fatty acids is important for overcoming cancer. Here, we attempted to synthesize conjugated fatty acids using enzymes extracted from seaweeds containing these fatty acids. Lipids from 12 species of seaweeds from the seas around Japan were analyzed, and Padina arborescens Holmes was found to contain conjugated fatty acids. Then, we synthesized parinaric acid, a conjugated tetraenoic acid, from α-linolenic acid using the enzyme of P. arborescens. This method is expected to have a variety of potential applications for overcoming cancer.
Topics: alpha-Linolenic Acid; Seaweed; Fatty Acids, Unsaturated; Antineoplastic Agents
PubMed: 38692896
DOI: 10.5650/jos.ess23209 -
The Journal of Physiology Jul 2017α-linolenic acid (ALA) and exercise training both attenuate hyperlipidaemia-related cardiovascular derangements, however, there is a paucity of information pertaining...
KEY POINTS
α-linolenic acid (ALA) and exercise training both attenuate hyperlipidaemia-related cardiovascular derangements, however, there is a paucity of information pertaining to their mechanisms of action when combined. We investigated both the independent and combined effects of exercise training and ALA consumption in obese Zucker rats, aiming to determine the potential for additive improvements in cardiovascular function. ALA and exercise training independently improved cardiac output, end-diastolic volume, left ventricular fibrosis and mean blood pressure following a 4 week intervention. Combining ALA and endurance exercise yielded greater improvements in these parameters, independent of changes in markers of oxidative stress or endogenous anti-oxidants. We postulate that divergent mechanisms of action may explain these changes: ALA increases peripheral vasodilation, and exercise training stimulates angiogenesis.
ABSTRACT
Although α-linolenic acid (ALA) and endurance exercise training independently attenuate hyperlipidaemia-related cardiovascular derangements, there is a paucity of information pertaining to their mechanisms of action and efficacy when combined as a preventative therapeutic approach. Therefore, we used obese Zucker rats to investigate the independent and combined effects of these interventions on cardiovascular disease. Specifically, animals were randomly assigned to one of the following groups: control diet-sedentary, ALA supplemented-sedentary, control diet-exercise trained or ALA supplemented-exercise trained. Following a 4 week intervention, although the independent and combined effects of ALA and exercise reduced (P < 0.05) the serum free/esterified cholesterol ratio, only the ALA supplemented-exercise trained animals displayed a reduction in the content of both serum free and esterified cholesterol. Moreover, although ALA and endurance training individually increased cardiac output, stroke volume and end-diastolic volume, as well as reduced left ventricle fibrosis, mean blood pressure and total peripheral resistance, these responses were all greater following the combined intervention (ALA supplemented-exercise trained). These effects occurred independent of changes in oxidative phosphorylation proteins, markers of oxidative stress or endogenous anti-oxidant capacity. We propose that the beneficial effects of a combined intervention occur as a result of divergent mechanisms of action elicited by ALA and endurance exercise because only exercise training increased the capillary content in the left ventricle and skeletal muscle, and tended to decrease protein carbonylation in the left ventricle (P = 0.06). Taken together, our data indicate that combining ALA and endurance exercise provides additional improvements in cardiovascular disease risk reduction compared to singular interventions in the obese Zucker rat.
Topics: Animals; Blood Pressure; Cardiovascular Diseases; Cholesterol; Diastole; Exercise Therapy; Heart Rate; Male; Obesity; Physical Conditioning, Animal; Rats; Rats, Zucker; alpha-Linolenic Acid
PubMed: 28345766
DOI: 10.1113/JP274036